This revised Mentored Patient-Oriented Research Career Development Award (K23) application is a request for funding to support the training and research activities necessary for David J. Moser, Ph.D. to become an independent investigator in aging, vascular disease, and cognition. Atherosclerotic vascular disease (AVD) is the leading cause of mortality and morbidity in most industrialized nations and is a primary contributor to cognitive decline in the elderly. Despite this, there are very few longitudinal studies of AVD-related cognitive decline and the factors that are most predictive of this process. The identification of individuals who are at greatest risk for such decline will have significant implications for the development of interventions to prevent or attenuate this important health problem. This application includes an integrated and multidisciplinary program of training and research that utilizes the resources of the Center on Aging, the General Clinical Research Center, the Human Cardiovascular Physiology Laboratory, and the Departments of Psychiatry, Internal Medicine, Neurology, Biostatistics, Epidemiology, and Pharmacy at the University of Iowa. Trained in neuropsychology, the applicant now requires additional training in aging, cardiovascular and cerebrovascular physiology, longitudinal multivariate research, analysis of neuroimaging data, ethics, and grantwriting. This training and the proposed research project will allow the applicant to meet the following short-term scientific goals: 1 ) Determine whether elderly individuals with atherosclerotic vascular disease demonstrate inferior baseline neurocognitive performance and greater neurocognitive decline across time, as compared to healthy controls; and 2) Determine whether degree of endothelial dysfunction and/or other vascular illness-related variables can be used to identify subjects at greatest risk for neurocognitive decline. The training and data obtained during the K23 funding period will lay the foundation for the applicant's long-term scientific goal, which is to have an independent program of research aimed at preventing and/or reducing vascular-related cognitive decline.